Project description:This SuperSeries is composed of the following subset Series: GSE18647: Gene expression in embryonic intervertebral disc and vertebrae. GSE18648: TGF-beta and BMP mediated gene expression in cultured sclerotome. Refer to individual Series
Project description:We used microarrays to detail the gene expression profile during WAT -beige transition by treatment of beta adrenergic receptor agonist .
Project description:Environmental cues, such as shear stress and heterotypic cell interactions play a critical role in endothelial cell function, yet their unique contributions to the endothelial cell transcriptome remain unclear. Using cell preparations from human umbilical cords (ex vivo), we performed individual sample analysis to assess transcriptional drifts associated with environmental changes but independent of sex or background. Global gene expression profiling by RNA-seq, ATACseq, and MS/MS directed proteomics distinguished freshly isolated endothelial cells from genetically matched culture (in vitro) samples. Over 43% of the transcriptome was significantly changed by the in vitro environment. Amongst several signatures, we observed that TGF-beta and BMP target genes were reduced. In contrast, cytoskeleton-based processes and proliferation-related genes were increased. Subjecting cultured cells to long-term shear stress significantly rescued the expression of approximately 17% of genes including targets of BMP and Notch signaling known to be sensitive to flow. In contrast, co-culture of endothelial cells with smooth muscle cells normalized networks related to cell growth and differentiation, clathrin-vesicle related genes, and recovered targets downstream TGF-beta, recovering approximately 9% of the original in vivo signature. Our findings highlight specific genes, pathways and functional features of endothelial cells that require contextual information and exposure to physical forces. This transcriptional modulation is important to consider in all paradigms that are focused on understanding the ability of endothelial cells to maintain homeostasis and respond to disease processes.
Project description:Gene-specific transcription factors (GSTFs) control of gene transcription by DNA binding and specific protein complex recruitment, which regulates promoter accessibility for transcription initiation by RNA polymerase II. GSTFs that are frequently mutated in colon and rectal carcinomas are Suppressor of Mothers Against Decapentaplegic 2 (SMAD2) and SMAD4, which play an important role in the TGF-β signaling pathways controlling cell fate and proliferation (ref.). The SMAD protein family is a diverse and it can be divided into three subclasses: receptor activated SMADs, inhibitory SMADs and the common SMAD4 co-activator. To study protein interactors of the SMAD protein family we generated a quantitative proteomics pipeline that allows for inducible expression of GFP-tagged SMAD proteins followed by affinity purification and MS analysis. The nuclear importin IPO5 was identified as a novel interacting protein of SMAD1. Overexpression of IPO5 shows forced BMP R-SMAD nuclear localization confirming a functional relationship between BMP but not TGF-β R-SMADs and IPO5. Finally we provide evidence that the length of the lysine stretch in the NLS is involved in importin selection.